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Pharmaceutical and Biotech News

Development News in 2010

(Page 3)

Pharmaceutical and Biotech News concentrates on events that mark progress (or failure) in the development of promising new treatments in challenging therapeutic areas.  The areas covered are as follows:

Oncology

Metabolic and inflammatory diseases and syndromes

Coagulation/anticoagulation

Bacterial, viral and fungal infections

Neurological disorders

In most cases, company announcements are dissected for pertinent facts; personal interviews and reviews by a variety of sites may be included;  occasional commentary -clearly marked as such- highlights specific compounds or clinical studies worthy of greater emphasis.  Marketed drugs, mentioned in these pages, will be linked, whenever possible, to their current US Package Inserts.

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December 20, 2010

FDA Proceeds to Remove the Breast Cancer indication from bevacizumab (Avastin®)

The FDA announced on December 16, 2010 that it is beginning the process to remove from bevacizumab the indication for the treatment of breast cancer.  The agency stated that the review of the results of four clinical studies of Avastin in breast cancer showed that the drug does not prolong overall survival and does not provide a sufficient benefit in slowing disease progression although it does possess significant risks and possible adverse reactions such as severe high blood pressure, bleeding, the development of perforations in the body (including in the nose, stomach, and intestines), and heart attack or heart failure. As we indicated here in a prior posting,  in July 2010, an independent advisory committee voted 12-1 to remove the breast cancer indication from Avastin’s label.   This has not been the only negative assessment of bevacizumab.  The UK-based National Institute of Health and Clinical Excellence (NICE) in a well-documented assessment also found no evidence to support the use of bevacizumab in combination with taxanes in the treatment of breast cancer.  The US FDA process of removing the indication would certainly be lengthy, including consultations with Roche/Genentech.

October 25, 2010

Interim Results from Randomized Phase 2 Trial of Oral Ridaforolimus in Advanced Endometrial Cancer

Ariad Pharmaceuticals announced interim of a randomized, open-label, active-control multicenter Phase 2 study of oral ridaforolimus, in patients with metastatic or recurrent endometrial cancer. Ridaforolimus, developed in association with Merck, is a targeted small-molecule inhibitor of the protein mTOR. mTOR, a popular target of anti-neoplastic drugs, acts as a central regulator of protein synthesis, cell proliferation, cell cycle progression and cell survival.

The interim analysis was based on 114 patients enrolled at 39 sites in North America and Europe. Patients in the trial were randomized to receive either oral ridaforolimus (n=57), or oral progestin (n=48) or chemotherapy (n=9), both standard treatments in patients with advanced endometrial cancer. Progression-free survival (PFS) was determined by evaluating tumor shrinkaged utilizing RECIST criteria based on radiologic studies conducted every two months. An independent review committee evaluated all of the radiologic studies. The interim analysis demonstrated a significant improvement in the study’s primary endpoint, PFS, with a statistically significant 1.7 month difference in median PFS (ridaforolimus, 3.6 months; standard of care, 1.9 months, p=0.007) and a hazard ratio of 0.52.  It should be, however, noted that improvements in PFS often fail to translate to improvements in overall survival (OS), the clinical benefit endpoint utilized in pivotal clinical studies.

The interim analysis also showed that the most common adverse events observed with ridaforolimus were mucositis (38.2%), stomatitis (21.8%) and hyperglycemia (27.3%), which have been observed in previous studies and are considered to be class effects of mTOR inhibitors. Overall, patients treated with ridaforolimus had significantly more serious adverse events (23.6%) than patients treated with the standard of care (3.8%).

October 18, 2010

Phase II study with ocrelizumab shows significant reduction in brain lesions and relapses  for multiple sclerosis patients

Ocrelizumab is a humanized monoclonal antibody designed to selectively target CD20-positive B-cells, which are believed to play a critical role in multiple sclerosis (MS). It then interacts with the body’s immune system to eliminate CD20-positive B-cells. It is jointly developed by Biogen-IDEC and Roche.

The companies announced 24-week results from a phase II study of ocrelizumab in patients with relapsing-remitting multiple sclerosis (RRMS), the most common form of the disease. The study is a randomized, multicenter, 220-patient clinical trial investigating ocrelizumab versus placebo in patients with RRMS although open-label, rater-blinded, interferon beta-1a (Avonex, 30 mcg IM) was also included as a study arm. Efficacy and safety profile of two dose regimens of ocrelizumab (600mg and 2000mg) were evaluated in this study. Patients were treated for 24 weeks and received two ocrelizumab intravenous infusions of 300mg or two intravenous infusions of 1000mg at day 1 and day 15. The primary efficacy endpoint was reduction in brain lesions compared to placebo.  Lesions were observed by magnetic resonance imaging (MRI) scans of the brain at weeks 12, 16, 20 and 24.

Ocrelizumab demonstrated a significant reduction in disease activity as measured by brain lesions and relapse rate. Reductions in total number of brain lesions detected by magnetic resonance imaging (MRI) scans (the primary endpoint of the study) were highly significant at 96% for 2000mg ocrelizumab and 89% for 600mg ocrelizumab compared to placebo . Disease activity was also measured by reduction in annualised relapse rate (ARR), the rate of attacks or flare-ups per patient-year. At week 24, ARR was significantly lowered versus placebo with a reduction of 73% for ocrelizumab 2000mg and 80% for ocrelizumab 600mg.

Both ocrelizumab doses were generally well tolerated and no opportunistic infections were reported.    Serious adverse events (SAEs) were similar in all treatment groups. Infusion-related events during first infusion, predominantly mild to moderate, were more common with ocrelizumab (34.5% and 43.6%) than placebo (9.3%). However, these reports decreased during the second ocrelizumab infusion and were comparable to those initially reported with placebo.

August 24, 2010

Pfizer's Sutent® fails to increase overall survival in previously treated patients diagnosed with non-small cell lung cancer (NSCLC):

Sutent® (sunitinib malate) is a multiple receptor tyrosine kinase inhibitor that has been approved for the treatment of kidney cell carcinoma and certain gastrointenstinal stromal tumors. In a Phase III study (SUN 1087) in which the efficacy and safety of sunitib plus erlotinib (Tarceva® - Genentech/OSI Oncology) was compared to that of erlotinib plus placebo, there was no statistical difference in overall survival.  A statistical difference was detected in a secondary endpoint, progression-free survival (PFS).  Patients enrolled in the SUN 1987 study were diagnosed with metastatic or locally advanced NSCLC and had received previous treatment including platinum chemotherapy.  Sutent® has recently failed in Phase III studies in advanced breast cancer and advanced hepatocellular carcinoma.

August 11, 2010

Amgen's Vectibix fails in a Phase III study in head and neck cancer:

Vectibix (panitumumab injection) is a monoclonal antibody that binds to the epidermal growth factor receptor (EGFR) and inhibits or slows down malignant cell proliferation.  Vectibix was  approved in 2006 by the FDA for the treatment of metastatic colon carcinoma.

Amgen's SPECTRUM study evaluated the safety and efficacy of Vectibix as a first-line treatment in patients with recurrent and/or metastatic squamous cell head and neck cancer. The study accessed 658 patients who were randomized to receive a standard platinum-based chemotherapy (cisplatin and 5-FU), with or without Vectibix (9 mg/kg) every three weeks. The primary endpoint was overall survival. The secondary endpoints included progression-free survival, objective response rate, duration of response, time to progression, time to response, patient reported outcomes and safety.

Analysis of the data showed the addition of Vectibix to platinum-based chemotherapy did not result in a statistically significant improvement in overall survival, the primary endpoint, compared to chemotherapy alone [median 11.1 months versus 9.0 months, hazard ratio 0.87 (95% CI: 0.73, 1.05)]. Therefore, the study did not meet its primary endpoint. Secondary endpoints of progression-free survival [median 5.8 months versus 4.6 months, hazard ratio 0.78 (95% CI: 0.66, 0.92)] and objective response rate (36 percent versus 25 percent) were numerically improved but were not tested for statistical significance.

 The most frequently reported adverse events in the Vectibix plus chemotherapy arm included nausea, rash, neutropenia and vomiting, as anticipated for this combination therapy.

July 27, 2010

Announcement of data from the Phase 2b study in multiple myeloma with Onyx' CarfilzomibCarfilzomib is a novel, irreversible, epoxomicin-related proteasome inhibitor. Proteasomes are very large protease complexes inside cells that degrade no longer required or damaged proteins.  Proteasome inhibitors induce apoptosis of malignant cells by disrupting the degradation of pro-growth proteins in these cells. 

Onyx's 003-A1 clinical study with carfilzomib was an open-label, single-arm Phase 2b trial. It evaluated 266 heavily-pretreated patients with relapsed and refractory multiple myeloma whose disease did not respond to their last treatment regimen and who had received at least two prior therapies, including bortezomib (another proteasome inhibitor by a reversible one), either thalidomide or lenalidomide, an alkylating agent, glucocorticoids and an anthracycline. Refractory disease was defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy. Patients enrolled in the trial had received a median of five prior therapeutic regimens, corresponding to a median of 13 anti-myeloma agents. Patients received carfilzomib at 20mg/m2 for the first cycle followed by 27mg/m2 thereafter for up to 12 cycles. Patients who completed the 12 cycles were eligible to enter an extension study. Responses and progression were determined according to the International Myeloma Working Group (IMWG) criteria. 

Following an independent review of the data, carfilzomib achieved an overall response rate (partial response or greater) of 24% and a median duration of response of 7.4 months. The clinical benefit rate (minimal response or greater) in the study population was 36%. Carfilzomib was well-tolerated and there were no new or unexpected toxicities observed.  Onyx announced that based on these results it is continuing discussions with the U.S. Food and Drug Administration (FDA) regarding filing a new drug application (NDA) for carfilzomib, which the company expects to submit by year-end 2010 for potential accelerated approval in the U.S.

July 27, 2010

The FDA's Oncologic Drug Advisory Committee recommends against the approval of Avastin in metastatic breast cancer: Bevacizumab (Avastin) is a humanized monoclonal antibody that blocks the vascular endothelial growth factor A (VEGF-A), a compound that stimulates the growth of new blood vessels (angiogenesis). It is approved for the treatment metastatic colon, non-small cell lung and renal cancers. The FDA granted accelerated approval for bevacizumab as first line treatment in metastatic breast cancer but this approval was contingent on additional positive results from ongoing clinical trials.

 In meeting on July 20, the advisory committee voted 12 to 1 to recommend against the use of Avastin in combination with chemotherapy as a first line treatment in metastatic breast cancer.  The data from the additional studies (AVADO and RIBBON1) failed to confirm the data from study E2100 that served as the basis of the original approval in metastatic breast cancer. The additional trials performed by Genentech, together enrolled almost 2,500 women. The women in AVADO were randomly assigned to receive chemotherapy with docetaxel plus placebo or docetaxel plus bevacizumab. The patients in the bevacizumab arm of AVADO had a median improvement in PFS of less than a month. In RIBBON1, patients were assigned at the discretion of their physicians to receive chemotherapy with a taxane, an anthracycline, or capecitabine (Xeloda). Within those three groups, the researchers randomly assigned women to receive additional bevacizumab or a placebo. The improvement in PFS was minor: just 1.2 months in the taxane and anthracycline groups and 2.9 months in the capecitabine group. In both trials, the bevacizumab groups exhibited an increased risk of death. According to the FDA presentation, FDA, 0.8 percent of the women in AVADO and 1.2 percent of the women in RIBBON1 who received bevacizumab died from side effects thought to be related to the drug.  Significantly, the meeting underlined the difficulty of interpreting Progression-Free Survival (PFS) as the primary endpoint of trials in oncology.

July 14, 2010

Biogen Idec and Swedish Orphan Biovitrum Announce Decision to Advance Long-Lasting Hemophilia A and B Therapies:

Biogen Idec and Swedish Orphan Biovitrum  today announced results of their program with their recombinant Fc-fusion hybrids of the coagulation Factors VIII and FIX.  The absence -or abnormally low levels- of these factors in blood cause hemophilia A and B, respectively.

The companies agreed to advance the recombinant factor VIII Fc fusion protein (rFVIIIFc) into a registrational clinical trial. The decision to advance the program is based on promising data from a Phase 1/2a open-label, cross-over, multi-center, dose-escalation study that evaluated the safety and pharmacokinetics of an intravenous injection of rFVIIIFc in 16 previously-treated hemophilia A patients (>100 exposure days) with severe hemophilia A. In the study, rFVIIIFc was well tolerated and demonstrated a prolonged half-life compared to Advate® (Baxter's 3rd generation rFVIII).  The primary objective of the Phase 1/2a study was to assess the safety of rFVIIIFc at different doses; secondary objectives included the estimation of the pharmacokinetic (PK) parameters of rFVIIIFc at doses ranging from 25 to 65 IU/kg. Preliminary results demonstrated that rFVIIIFc's prolonged half-life compared to Advate® was seen consistently across all patients and dose levels, and other measures of pharmacokinetics including mean residence time and area under the curve were also increased. There were no signs of injection site reactions, inhibitor development (in previously treated patients) or anti-rFVIIIFc drug antibodies in the single-dose study, and there have been no reports of drug-related serious adverse events.  The preliminary data appear to be in agreement with the half-life prolongation seen in a population of hemophilia A dogs presented in last year's ASH meeting.

In addition to the data with FVIIIFc, Biogen Idec  and Orphan Biovitrum AB announced results from a Phase 1/2a open-label, dose-escalation, safety and pharmacokinetic study of the companies' recombinant factor IX Fc fusion protein (rFIXFc) in hemophilia B patients. The data, which were presented at the World Federation of Hemophilia Congress in Buenos Aires, Argentina, on July 11, 2010, showed that rFIXFc was well tolerated and demonstrated an approximately three-fold increase in half-life compared to historical data for existing therapies.  This was in line with previously published data in a number of animal models.

Increasing the terminal half-life of FVIII (approximately 10 - 12 hours) and FIX (approximately 18 hours)  has been an important goal in hemophilia treatment.  Over the last decade, long-term prophylaxis has become the state of the art in hemophilia treatment, limiting damage to joints and improving quality of life.  However, frequent infusions (2-3 times weekly) and problems/complications with venous access make long-term prophylaxis daunting for patients.  Improving the terminal half-lives of these clotting factors would facilitate adherence and have substantial impact on patients' quality of life and overall health maintenance. Although the results so far have been encouraging, pivotal studies of these two fusion proteins would investigate their efficacy and safety in long-term prophylaxis (> 50 - 75 exposure days).  Breakthrough bleeding rates and inhibitor development should be on par with current concentrates.  The development of inhibitors both in previously treated and untreated hemophilia patients is a serious complication, leading to difficult and expensive treatment considerations.

June 4 - 8, 2010

ASCO 2010

There were various announcements at the recent ASCO meeting (June 4 -8, Chicago, IL) regarding existing and novel drugs for the treatment of various malignancies.  I have emphasized selectively specific agents and clinical studies that provide substantial promise for new or improved therapeutic approaches in a special page called  ASCO 2010. In that page, I have included a general summary -from my perspective, of course- as well as selected announcements for which my usual approach is applied (pertinent facts are selected, company spin is discounted and my comments are clearly indicated). 

June 3, 2010

Pivotal Phase III Trial of Afinitor Met Primary Endpoint in Study of Patients With Advanced Pancreatic Neuroendocrine Tumors: Afinitor (everolimus) is an inhibitor of the the mTOR protein, an important target in various cancers.  It is being developed by Novartis.  In 2009, it obtained approval in the treatment of kidney cancer resistant to sorafenib (Nexavar) or sunitinib (Sutent). The phase III study (RADIANT-3) in pancreatic endocrine tumors (a rare but aggressive malignancy with few treatment options) was  double-blind, randomized, parallel group, placebo-controlled, multicenter study. The trial compared the efficacy and safety of everolimus plus best supportive care against placebo plus best supportive care in 410 patients with advanced pancreatic NET. Patients who met the study's entry criteria were randomized 1:1 to receive either daily everolimus (10 mg) or daily placebo orally.  Progression-free survival was the main endpoint of the study, with objective response and overall survival as secondary endpoints.

May 19, 2010

Roche and Biogen Idec Announce Decision to Discontinue Phase 3 Ocrelizumab Clinical Development Program in Patients with Rheumatoid Arthritis: Ocrelizumab is a humanized monoclonal antibody that disrupts the inflammatory cascade in rheumatoid arthritis (RA) by selectively targeting CD20 positive B cells.  Such activity relieves symptoms and prevents irreversible joint damage which can be very severe in affected patients.  The phase 3 program for ocrelizumab included four studies (SCRIPT, FILM, FEATURE, and STAGE). The clinical program was discontinued because of the high rate of opportunistic infections in patients receiving the drug.  Biogen Idec is still continuing the testing of this humanized antibody in multiple sclerosis in a collaboration agreement with Genentech.

May 7, 2010

Bayer Schering Pharma commences Phase III clinical study with regorafenib in metastatic colorectal carcinoma:  Regorafenib (or BAY 73-4506) is a small molecule inhibitor of endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases.  Regorafenib has shown substantial promise in the treatment of previously untreated patients with metastatic or unresectable renal cell carcinoma.  Regorafenib is structurally very similar to sorafenib (Nexavar®) which Bayer is marketing (and developing) in association with Onyx Pharmaceuticals. The close similarity in structure (the addition of a single fluorine atom in Regorafenib) prompted a legal challenge by Onyx. The upcoming Phase III clinical study in metastatic colorectal carcinoma will enroll approximately 690 patients who have failed standard treatment and compare overall survival of patients treated with regorafenib vs. those treated with placebo.

April 30, 2010

FDA approves PROVENGE® for the treatment of asymptomatic of minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer: PROVENGE® (sipuleucel-T) is a autologous cellular immunotherapy in which the patient's own CD54+ cells are utilized after treatment with a recombinant protein, PAP-GM-CSF.  PAP-GM-CSF consists of the prostatic acid phosphatase (PAP), an enzyme expressed in prostate cancer tissue, linked to granulocyte-macrophage colony stimulating factor (GM-CSF).  In two pivotal studies utilizing 639 patients, PROVENGE® extended overall survival by approximately 5 months.   PROVENGE® is marketed by Dendreon, a Seattle, WA -based company.

April 22, 2010

Pfizer ends trial of Sutent in liver cancer Sutent® (sunitinib malate) is a receptor tyrosine kinase inhibitor that has been approved for the treatment of kidney cell carcinoma and certain gastrointenstinal stromal tumors. In a Phase 3 study (SUN 1170) of Sutent® vs. Nexavar® (sorafenib) in patients diagnosed with advanced hepatocellular carcinoma, Sutent® failed to demonstrate either superiority or non-inferiority to Nexavar® in overall survival. In addition, there was a higher incidence of serious adverse events in the Sutent® arm. Recently, Sutent® failed in Phase 3 studies in advanced breast cancer, but pivotal studies in advanced non-small cell lung cancer, advanced castration-resistant prostate cancer, and as an adjuvant treatment in kidney cancer are ongoing.

April 19, 2010

FDA Approves Tarceva as a Maintenance Therapy for Advanced Non-Small Cell Lung Cancer: Tarceva® (erlotinib) is a tyrosine kinase inhibitor acting on the epidermal growth factor receptor (EGFR).  Tarceva® has been previously approved for the treatment of locally advanced (metastatic) non-small cell lung cancer (NSCLC) and, in combination with gemcitabine, in metastatic pancreatic cancer.  It is co-marketed by OSI Pharmaceuticals and Genetech. The latest approval was based on the results of the Phase 3 SATURN clinical study.  In that study, patients diagnosed with NSCLC were treated with four cycles of standard first-line platinum-based chemotherapy and then randomized to Tarceva® or placebo if the cancer did not progress. The primary endpoint of the study was progression-free survival (PFS).  It was defined as the length of time from randomization to disease progression or death from any cause. Patients randomized to Tarceva® showed 41% improvement in the likelihood of living without the disease getting worse (PFS, the primary endpoint) compared to placebo (hazard ratio=0.71, 29 percent reduction in the risk of cancer progression or death, p<0.0001). Overall survival (OS) was improved by 23% with compared to placebo (hazard ratio=0.81, 19 percent reduction in the risk of death, p=0.0088). The most common reported adverse events associated with Tarceva® as maintenance therapy were rash (49%) and diarrhea (20%).

April 15, 2010

Idenix Pharmaceuticals Reports Positive Results With IDX184 From Interim Analysis of Phase IIa Hepatitis C Study: IDX184 is a nucleoside polymerase inhibitor developed by Idenix .  The ongoing phase IIa clinical trial is a double-blind, sequential dose-escalation study to evaluate the safety and efficacy of IDX184 in combination with pegylated interferon(pegIFN) and ribavirin in HCV genotype 1-infected patients versus placebo (plus pegIFN/ribavirin). Treatment consists of a daily dose of IDX184 or placebo, plus pegIFN/ribovarin for 14 days and then PegIFN/ribavarin for an additional 14 days.  In the data presented today, IDX184 demonstrated dose-dependent antiviral activity.  Half of the subjects receiving a total daily dose of 100 mg IDX184 achieved undetectable virus levels (< 15 IU/mL) by Day 14. Liver injury parameters (ALT and AST) improved (normalized) with all doses of IDX184. The adverse experience (AE) profile of the three-drug combination was consistent with the known AE profile of PegIFN/ribavarin alone. The most common adverse events reported were fatigue, myalgia, headache and nausea.

Comment: Treatment of HCV is an extremely active area of drug development with approximately 140 drugs in development currently.  Major pharmaceutical and smaller biotech companies are pursuing various compounds that include, among others, protease polymerase inhibitors and nonstructural protein 5A (NS5A) inhibitors and therapeutic vaccines.

April 14, 2010

Baxter International reports data from a Phase 2 study of Gammagard® in Alzheimer's disease: Gammagard®, Baxter's intravenous human immunoglobulin concentrate, was evaluated in patients with mild-to-moderate Alzheimer's disease in a limited double-blind, placebo-controlled Phase 2 study.  Enrolled patients (n = 24) received either Gammagard® or placebo intravenously for a period of 6 months followed by a 4-6 week washout period.  After this period, patients were maintained on Gammagard® for a total treatment period of 18 months. Cognition and function were assessed by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale score (ADAS-Cog) and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale (ADCS-CGIC). After 18 months, patients who received Gammagard® continuously (n=14) averaged approximately 1.36 points higher than patients (n=7) who initially received placebo (-0.64 vs. -2.0, p=0.011) on the ADCS-CGIC. Also, the patients who received Gammagard® continuously declined by approximately 9.15 fewer ADAS-Cog points than patients who initially received placebo (approximately 6 point decline vs. 15 point decline, p=0.013).  Patients treated continuously with Gammagard® also showed improvement in secondary outcome measures such as lower ventricular enlargement rates in their brains and lower mean annual whole brain atrophy.  Brain atrophy rates correlated with clinical outcomes.  A Phase 3 study of Gammagard® (the Gammaglobulin Alzheimer’s Partnership (GAP) Study) is currently ongoing.

Genzyme reports follow-up data from the Phase 2 study of alemtuzumab in multiple sclerosis (MS): Alemtuzumab is a monoclonal antibody that targets in a selective fashion, targets T- and B-lymphocytes while largely sparing other immune system elements. These lymphocytes mistakenly attack the myelin sheath that protects nerve cells in MS patients.  The phase 2 study compared annual treatments cycles with alemtuzumab to subcutaneous interferon beta-1a (Rebif®)at a dose of 44 µg three times per week. Treatment was to last for three years.  The study commenced in 2002 but alemtuzumab treatment was discontinued in 2005 because 3 patients developed immune thrombocytopenic purpura (ITP), one of whom died. Results of the study, published in NEJM in 2008, illustrated that alemtuzumab  reduced significantly the rate of sustained accumulation of disability as compared with interferon beta-1a (9.0% vs. 26.2%) but was associated with autoimmunity, manifesting as immune thrombocytopenic purpura. The follow-up four-year data show that an estimated 71% of alemtuzumab-treated patients were free of clinically-active disease, compared to 35 percent of patients taking Rebif® (p<0.001). Overall, six alemtuzumab treated patients and one Rebif patient in the Phase 2 trial have developed ITP. Approximately 28 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event. Genzyme is currently performing two phase 3 studies with alemtuzumab.

InterMune Reports Top-Line Results From Phase 2b Study of Danoprevir in Patients with Chronic Hepatitis C: Danoprevir (also known as RG7227 or ITMN-191) is macrocyclic inhibitor of HCV NS3/4A protease activity. The Phase 2b clinical trial reported was a randomized, partially-blind study evaluating danoprevir, administered for 12 weeks in combination with Pegasys® (pegylated interferon alfa-2a) and Copegus® (ribavirin), compared with placebo plus Pegasys® and Copegus® for the same period of time. Three doses/dose regimens of danoprevir (300 mg -q8hr, 600 mg - q12hr, 900mg - q12hr) were tested.  At 12-weeks, patients with virologic response were 88%, 89% and 92% of participating subjects, respectively, vs. 43% for placebo + ribavirin + pegylated interferon.  Safety was comparable in all groups.  Intermune is developing danoprevir in association with Roche.  The companies announced that future studies of danoprevir will examine its efficacy when administered in lower doses in combination with ritonavir (Norvir®), a currently marketed protease inhibitor.

April 13, 2010

ChemGenex Receives a Complete Response Letter from the FDA for Omapro™: Omapro™ (Omacetaxine mepesuccinate)  induces apoptosis by inhibition of protein synthesis, particularly Mcl-1. It is being evaluated in clinical trials in a range of hematological malignancies.  ChemGenex submitted an NDA for the use of Omapro™ in chronic myeloid leukemia (CML) in September 2009.  The company did not reveal details regarding the contents of the Complete Response letter, although it stated that the FDA did not request additional studies.  Some of the criticism of the Omapro™ pivotal study in CML can be found in minutes of the meeting of the Oncologic Drugs Advisory Committee held in March 22, 2010.  The main concerns during this meeting were (a) a small, incomplete and single trial in support of the indication, (b) one third of the patients in the study did not meet enrollment criteria, (c) low response rates, (d) variability in assays testing eligibility and (e) certain safety concerns.

April 12, 2010

Positive Results of the 2nd Phase 3 Study of Fidaxomicin for the Treatment of Clostridium difficile Infection (CDI): Fidaxomicin is represents a new class of antibiotics called macrocycles, which inhibit  bacterial RNA polymerases. It targets Clostridium difficile narrowly, without disturbing the typical intestinal flora. It is developed by Optimer Pharmaceuticals, Inc.  The final Phase 3 compared fidaxomicin to vancomycin in 535 adult subjects with confirmed C. difficile infection. The study met the primary endpoint of non-inferiority to vancomycin for the 10-day treatment period.  However fidaxomicin showed statistically lower recurrence rates compared to Vancocin (p = 0.002), and significantly higher global cure rates (defined as cure with no recurrence within four weeks of completing therapy) compared to vancomycicin (p < 0.001).

April 9, 2010

Roche and Biogen-Idec apply to expand Rituxan label Rituxan® (rituximab) is a genetically engineered chimeric murine/human monoclonal IgG antibody directed against the CD20 antigen expressed in B lymphocytes.  It is approved for the treatment of Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia (CLL) and Rheumatoid Arthritis.  Roche and Biogen-Idec submitted a supplemental Biologics License Application (sBLA) to FDA to expand the usage of Rituxan in the maintenance therapy of previously untreated patients with advanced follicular lymphoma.  The data for the supplemental application were derived from the Phase 3 PRIMA study, the results of which were announced last September.

April 8, 2010

Aeterna Zentaris Announces Initiation of Phase 3 Registration Trial with Perifosine in Refractory Advanced Colorectal CancerPerifosine is an alkylphospholipid exhibiting antitumor properties by acting on the Akt and other signal transduction pathways such as JNK and MAPK.  It induces apoptosis although its mechanism of action is still undefined.  The Phase 3 study protocol will compare overall survival of patients with refractory advanced colorectal cancer treated with perifosine + Xeloda vs those treated with placebo + Xeloda. Perifosine is also developed in multiple myeloma (a Phase 3 study is ongoing).  Aeterna Zendaris has outlicensed perifosine in North America to Keryx Biopharmaceuticals, which oversees the clinical development program.

April 1, 2010

The Clinical Potential of MediciNova's MN-166 Featured in Neurology Articles: MN-166 (Ibudolast: 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine)) is an anti-inflammatory compound acting mainly as a phosphodiesterase inhibitor.  The compound has been licensed in Japan since 1989. A US patent filed in 2001 and issued in 2002 for its utility in neuroprotection prompted its development in multiple sclerosis (MS).  The public release by MediciNova refers to a recent publication in "Neurology" of an article summarizing the results of a phase 2 clinical trial.  The trial in 297 patients with recurring, relapsing MS showed that although the compound did not have any effect in relapse rate or lesion appearance, it was more successful than control in reducing percentage brain volume change (PBVC) and preventing lesions in becoming persistent black holes (a post hoc analysis).  No further clinical trials are ongoing in this indication.

March 30, 2010

PolyMedix Successfully Completes Phase 1B Clinical Study With Novel Antibiotic PMX-30063 (by Businesswire). PMX-30063 a small molecule mimetic of human host-defense proteins.  The company claims that this antibiotic possesses unique advantages such as (a) mechanism of action directed at the biophysical disruption of bacterial cell membranes which may make resistance difficult to evolve (b) Activity against both Gram-positive and Gram- negative bacteria, and (c) activity against 146 different strains of Staphylococcus bacteria, including drug-resistant strains of Staph bacteria (MRSA).  PolyMedix, a Pennsylvania-based company is developing a number of anti-infective compounds.

March 30, 2010

PolyMedix Successfully Completes Phase 1B Clinical Study With Novel Antibiotic PMX-30063 (by Businesswire). PMX-30063 a small molecule mimetic of human host-defense proteins.  The company claims that this antibiotic possesses unique advantages such as (a) mechanism of action directed at the biophysical disruption of bacterial cell membranes which may make resistance difficult to evolve (b) Activity against both Gram-positive and Gram- negative bacteria, and (c) activity against 146 different strains of Staphylococcus bacteria, including drug-resistant strains of Staph bacteria (MRSA).  PolyMedix, a Pennsylvania-based company is developing a number of anti-infective compounds.

March 29, 2010

GenVeC discontinues Phase 3 clinical trial of TNFerade™ after interim analysis of the data in pancreatic cancer.  TNFerade is an adenovirus vector which contains the gene for tumor necrosis factor-alpha (TNFα), an immune system protein with anti-tumor activity.  TNFerade is directly injected into the tumor where it stimulates expression of TNFα.  This agent is utilized in conjunction with standard chemotherapy or radiation.  TNFerade was also being tested in head and neck cancer, but it appears that this program is discontinued.  The company announced that it will focus in the development of its vaccines.

Regulus Therapeutics Publish Pre-clinical In Vivo Efficacy Data on microRNA Therapeutics targeting microRNA-10b in Models of Breast Cancer Metastasis.  MicroRNAs are recently-discovered non-coding RNAs of about 22 nucleotides in length that regulate the expression of specific genes. There is intense interest in positively defining the role of microRNAs in cancer and developing blocking or modulating agents.  So far, progress has been less than spectacular.  Regulus Therapeutics, a Carlsbad, California -based company, is developing oligonucleotide-based therapeutic agents that modulate the activity of microRNAs. The published data showed that treatment of breast tumor-bearing mice with a microRNA therapeutic inhibited metastasis.  

March 23, 2010

Merck Serono suspends trials with Oncothyreon's Stimuvax.  Stimuvax is a cancer vaccine designed to induce immune response to tumors expressing the MUC1 antigen. The suspension occurred because a multiple myeloma patient in one of the exploratory studies developed encephalitis. Phase 3 clinical trials in non-small cell lung carcinoma and breast cancer have also been suspended. 

March 22, 2010

Advaxis Immunotherapeutic ADXS11-001 Phase 1 Survival Data Extended (through BusinessWire): ADXS1-001 is under development in patients with advanced cervical cancer who have failed prior chemotherapy. Advaxis is a biotechnology company developing proprietary immunotherapeutics that deliver engineered tumor antigens, which stimulate multiple, simultaneous, immunological mechanisms to fight cancer.  The company has a number of these constructs under development.

FDA Advisory Panel votes unanimously against approval of Cell Therapeutics pixantrone.  Pixantrone is currently being developed for the treatment of patients with relapsed or refractory aggressive non-Hodgkin's lymphoma ("NHL") that have failed at least two previous courses of treatment. It is is a topoisomerase II inhibitor with an aza-anthracenedione molecular structure.  Regarding the rejection by the advisory panel, it is important to note that Cell Therapeutics, Inc. discontinued the Phase III study of pixantrone at an unscheduled time point due to poor enrollment.  The FDA's re-analysis of the data submitted by the company did not support a statistically significant treatment effect.  Apparently, the advisory panel shared the FDA's reservations.

March 17, 2010

ABRAXANE Meets Primary Endpoint in Phase 3 Trial for Advanced Non-Small Cell Lung Cancer (through BusinessWire): ABRAXANE® is protein-bound paclitaxel marketed by Abraxis Bioscience, Inc.   ABRAXANE® has already been approved for the treatment of metastatic breast cancer.